Prospective virologic studies at the University of Minnesota have shown that cytomegalovirus (CMV) is the most common cause of infection after renal transplantation. Although its importance is clear, there are gaps in our knowledge of the epidemiology, immunology, and prevention of CMV infection. We will address these gaps with 3 specific aims. 1) We will perform epidemiologic studies of posttransplant CMV infections to determine the importance of reactivation of endogenous virus, person-to-person spread, and presence of CMV DNA in donor kidneys. These studies will be accomplished by restriction endonuclease digestion to identify CMV strains, and DNA hybridization to search for CMV DNA in tissues. A 5-year serosurvey of personnel, student nurses, and blood donors is planned to examine patient-to-staff transmission of CMV on the transplant service. 2) We will perform a comprehensive prospective study of CMV-specific humoral and cell-mediated immunity in selected patients. Tests will include CMV antibody titers, lymphocyte proliferation to CMV antigen, monocyte T-cell interaction, natural killer cell and antibody-dependent cellular cytotoxicity and in vitro B-cell activation. Our aim is to define specific defects associated with susceptibility to posttransplant CMV. 3) We will complete our placebo-controlled evaluation of Towne CMV vaccine. Vaccine efficacy will be assessed and evidence of vaccine reactivation will be sought by endonuclease digestion analysis of plaque-purified isolates from any vaccinee who sheds CMV.